Search for other papers by Dafydd Aled Rees in
Google Scholar
PubMed
Search for other papers by Deborah P Merke in
Google Scholar
PubMed
Search for other papers by Wiebke Arlt in
Google Scholar
PubMed
Search for other papers by Aude Brac De La Perriere in
Google Scholar
PubMed
Search for other papers by Angelica Linden Hirschberg in
Google Scholar
PubMed
Search for other papers by Anders Juul in
Google Scholar
PubMed
Search for other papers by John Newell-Price in
Google Scholar
PubMed
Search for other papers by Alessandro Prete in
Google Scholar
PubMed
Search for other papers by Nicole Reisch in
Google Scholar
PubMed
Search for other papers by Nike M Stikkelbroeck in
Google Scholar
PubMed
Search for other papers by Philippe A Touraine in
Google Scholar
PubMed
Search for other papers by Alex Lewis in
Google Scholar
PubMed
Search for other papers by John Porter in
Google Scholar
PubMed
Search for other papers by Helen Coope in
Google Scholar
PubMed
Search for other papers by Richard J Ross in
Google Scholar
PubMed
Background
Prednisolone and prednisone are recommended treatment options for adults with congenital adrenal hyperplasia (CAH); however, there is no randomised comparison of prednis(ol)one with hydrocortisone.
Design
Six-month open-label randomised phase 3 study and interim analysis of a single-arm extension study was the design of the study.
Methods
The method of the study was hydrocortisone dose equivalent and 09:00-h 17-hydroxyprogesterone (17OHP) from 48 patients taking prednis(ol)one at baseline.
Results
At baseline, the median hydrocortisone dose equivalent was 30 mg/day and 17OHP was < 36 nmol/L (3× upper limit of normal) in 56% of patients. Patients were randomised to continue prednis(ol)one or switch to modified-release hydrocortisone capsule (MRHC) at the same hydrocortisone-equivalent dose. At 4 weeks, 94% on MRHC and 71% on prednis(ol)one had 17OHP < 36 nmol/L. At 18 months in the extension study of MRHC, the median MRHC dose was 20 mg/day and 82% had 17OHP < 36 nmol/L. The per cent of patients with 17OHP < 36 nmol/L on a hydrocortisone dose equivalent ≤ 25 mg/day was greater at 18 months in the extension study on MRHC than while on prednis(ol)one at baseline: 57% vs 27%, P = 0.04. In the randomised study, no patients had an adrenal crisis on MRHC and one on prednisolone. In the extension study (221 patient years), there were 12 adrenal crises in 5 patients (5.4/100 patient years).
Conclusion
MRHC reduces 17OHP at 09:00 h compared to prednis(ol)one and the dose of MRHC can be down-titrated over time in the majority of patients.
Search for other papers by Clara Lundetoft Clausen in
Google Scholar
PubMed
Search for other papers by Trine Holm Johannsen in
Google Scholar
PubMed
Search for other papers by Niels Erik Skakkebæk in
Google Scholar
PubMed
Search for other papers by Hanne Frederiksen in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Anders Juul in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Thomas Benfield in
Google Scholar
PubMed
In the context of severe coronavirus disease 2019 (COVID-19) illness, we examined endogenous glucocorticoid concentrations, steroidogenic enzyme activity, and their correlation with inflammation and patient outcomes. This observational study included 125 hospitalized COVID-19 patients and 101 healthy individuals as a reference group. We utilized LC-MS to assess serum concentrations of 11-deoxycortisol, cortisol, and cortisone, as well as activities of steroidogenic enzymes (11β-hydroxylase and 11β-hydroxysteroid-dehydrogenase type 1). Cox proportional hazards regression analysis and competing risk analysis were employed to analyze associations between glucocorticoid concentrations and outcomes, adjusting for relevant factors. In patients with COVID-19, cortisol concentrations were higher and cortisone concentrations were lower compared to the reference group, while 11-deoxycortisol concentrations were similar. Steroidogenic enzyme activity favored cortisol production. Correlations between glucocorticoid concentrations and inflammatory markers were low. A doubling in concentrations cortisol, was associated with increased 90-day mortality and mechanical ventilation (HR: 2.40 95% CI: (1.03–5.59) , P = 0.042 and HR: 3.83 (1.19–12.31), P = 0.024). A doubling in concentrations of 11-deoxycortisol was also associated to mortality (HR: 1.32 (1.05–1.67), P = 0.018), whereas concentrations of cortisone were associated with mechanical ventilation (HR: 5.09 (1.49–17.40), P = 0.009). In conclusion, serum concentrations of glucocorticoid metabolites were altered in patients hospitalized with severe COVID-19, and steroidogenic enzyme activity resulting in the conversion of cortisone to biologically active cortisol was preserved, thus not favoring critical-illness-related corticosteroid insufficiency at the enzymatic level. Glucocorticoid release did not counterbalance the hyperinflammatory state in patients with severe COVID-19. High serum concentrations of 11-deoxycortisol and cortisol were associated with 90-day mortality, and high serum concentrations of cortisol and cortisone were associated with mechanical ventilation.
Search for other papers by Arno Téblick in
Google Scholar
PubMed
Search for other papers by Ilse Vanhorebeek in
Google Scholar
PubMed
Search for other papers by Inge Derese in
Google Scholar
PubMed
Search for other papers by An Jacobs in
Google Scholar
PubMed
Search for other papers by Renata Haghedooren in
Google Scholar
PubMed
Search for other papers by Sofie Maebe in
Google Scholar
PubMed
Search for other papers by Gerdien A Zeilmaker-Roest in
Google Scholar
PubMed
Search for other papers by Enno D Wildschut in
Google Scholar
PubMed
Search for other papers by Lies Langouche in
Google Scholar
PubMed
Search for other papers by Greet Van den Berghe in
Google Scholar
PubMed
In critically ill adults, high plasma cortisol in the face of low ACTH coincides with high pro-opiomelanocortin (POMC) levels. Glucocorticoids further lower ACTH without affecting POMC. We hypothesized that in pediatric cardiac surgery-induced critical illness, plasma POMC is elevated, plasma ACTH transiently rises intraoperatively but becomes suppressed post-operatively, and glucocorticoid administration amplifies this phenotype. From 53 patients (0–36 months), plasma was obtained pre-operatively, intraoperatively, and on post-operative days 1 and 2. Plasma was also collected from 24 healthy children. In patients, POMC was supra-normal pre-operatively (P < 0.0001) but no longer thereafter (P > 0.05). ACTH was never high in patients. While in glucocorticoid-naive patients ACTH became suppressed by post-operative day 1 (P < 0.0001), glucocorticoid-treated patients had already suppressed ACTH intraoperatively (P ≤ 0.0001). Pre-operatively high POMC, not accompanied by increased plasma ACTH, suggests a centrally activated HPA axis with reduced pituitary processing of POMC into ACTH. Increasing systemic glucocorticoid availability with glucocorticoid treatment accelerated the suppression of plasma ACTH.
Significance statement
Glucocorticoids are often administered during pediatric cardiac surgery. In critically ill children, endogenous systemic glucocorticoid availability is elevated already upon ICU admission while ACTH levels are normal. This hormonal constellation suggests the presence of active feedback inhibition of ACTH. In this study, we have documented that intraoperative administration of glucocorticoids accelerates the suppression of ACTH, resulting in low plasma ACTH already upon ICU admission. Pre-operative plasma POMC, the ACTH precursor, but not ACTH, was increased. This is compatible with a centrally activated HPA axis prior to surgery in young children but reduced processing of POMC into ACTH within the pituitary. These findings suggest that glucocorticoid treatment in the context of pediatric cardiac surgery may amplify pre-existing impaired pituitary processing of the prohormone POMC.
Search for other papers by M Cherenko in
Google Scholar
PubMed
Search for other papers by N M Appelman-Dijkstra in
Google Scholar
PubMed
Search for other papers by A L Priego Zurita in
Google Scholar
PubMed
Search for other papers by N R Biermasz in
Google Scholar
PubMed
Search for other papers by O M Dekkers in
Google Scholar
PubMed
Search for other papers by F A Klok in
Google Scholar
PubMed
Search for other papers by N Reisch in
Google Scholar
PubMed
Search for other papers by A Aulinas in
Google Scholar
PubMed
Search for other papers by B Biagetti in
Google Scholar
PubMed
Search for other papers by S Cannavo in
Google Scholar
PubMed
Search for other papers by L Canu in
Google Scholar
PubMed
Search for other papers by M Detomas in
Google Scholar
PubMed
Search for other papers by F Devuyst in
Google Scholar
PubMed
Search for other papers by H Falhammar in
Google Scholar
PubMed
Search for other papers by R A Feelders in
Google Scholar
PubMed
Search for other papers by F Ferrau in
Google Scholar
PubMed
Search for other papers by F Gatto in
Google Scholar
PubMed
Search for other papers by C Grasselli in
Google Scholar
PubMed
Search for other papers by P van Houten in
Google Scholar
PubMed
Search for other papers by C Hoybye in
Google Scholar
PubMed
Search for other papers by A M Isidori in
Google Scholar
PubMed
Search for other papers by A Kyrilli in
Google Scholar
PubMed
Search for other papers by P Loli in
Google Scholar
PubMed
Search for other papers by D Maiter in
Google Scholar
PubMed
Search for other papers by E Nowak in
Google Scholar
PubMed
Search for other papers by R Pivonello in
Google Scholar
PubMed
Search for other papers by O Ragnarsson in
Google Scholar
PubMed
Search for other papers by R V Steenaard in
Google Scholar
PubMed
Search for other papers by N Unger in
Google Scholar
PubMed
Search for other papers by A van de Ven in
Google Scholar
PubMed
Search for other papers by S M Webb in
Google Scholar
PubMed
Search for other papers by D Yeste in
Google Scholar
PubMed
University of Glasgow, Office for Rare Conditions, Glasgow, UK
University of Glasgow, Developmental Endocrinology Research Group, Royal Hospital for Children, Glasgow, UK
Search for other papers by S F Ahmed in
Google Scholar
PubMed
Search for other papers by A M Pereira in
Google Scholar
PubMed
Background
Patients with Cushing syndrome (CS) are at increased risk of venous thromboembolism (VTE).
Objective
The aim was to evaluate the current management of new cases of CS with a focus on VTE and thromboprophylaxis.
Design and methods
A survey was conducted within those that report in the electronic reporting tool (e-REC) of the European Registries for Rare Endocrine Conditions (EuRRECa) and the involved main thematic groups (MTG’s) of the European Reference Networks for Rare Endocrine Disorders (Endo-ERN) on new patients with CS from January 2021 to July 2022.
Results
Of 222 patients (mean age 44 years, 165 females), 141 patients had Cushing disease (64%), 69 adrenal CS (31%), and 12 patients with ectopic CS (5.4%). The mean follow-up period post-CS diagnosis was 15 months (range 3–30). Cortisol-lowering medications were initiated in 38% of patients. One hundred fifty-four patients (69%) received thromboprophylaxis (including patients on chronic anticoagulant treatment), of which low-molecular-weight heparins were used in 96% of cases. VTE was reported in six patients (2.7%), of which one was fatal: two long before CS diagnosis, two between diagnosis and surgery, and two postoperatively. Three patients were using thromboprophylaxis at time of the VTE diagnosis. The incidence rate of VTE in patients after Cushing syndrome diagnosis in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years.
Conclusion
Thirty percent of patients with CS did not receive preoperative thromboprophylaxis during their active disease stage, and half of the VTE cases even occurred during this stage despite thromboprophylaxis. Prospective trials to establish the optimal thromboprophylaxis strategy in CS patients are highly needed.
Significance statement
The incidence rate of venous thromboembolism in our study cohort was 14.6 (95% CI 5.5; 38.6) per 1000 person-years. Notably, this survey showed that there is great heterogeneity regarding time of initiation and duration of thromboprophylaxis in expert centers throughout Europe.
National Institute of Endocrinology CI Parhon, Bucharest, Romania
Search for other papers by Sofia Maria Lider Burciulescu in
Google Scholar
PubMed
National Institute of Endocrinology CI Parhon, Bucharest, Romania
Search for other papers by Monica Livia Gheorghiu in
Google Scholar
PubMed
Search for other papers by Andrei Muresan in
Google Scholar
PubMed
National Institute of Endocrinology CI Parhon, Bucharest, Romania
Search for other papers by Iuliana Gherlan in
Google Scholar
PubMed
Search for other papers by Attila Patocs in
Google Scholar
PubMed
National Institute of Endocrinology CI Parhon, Bucharest, Romania
Search for other papers by Corin Badiu in
Google Scholar
PubMed
Background
Pheochromocytomas (PHEOs) are rare catecholamine-secreting adrenal tumors. Approximately 60–90% of bilateral PHEOs are hereditary. We retrospectively analyzed the clinical characteristics of patients with bilateral PHEOs and the morbidity rate (malignancy, tumor recurrence and adrenal insufficiency (AI) rate) related to surgery technique and genetic status of the patients.
Results
Fourteen patients (12.5%, nine women, five men) had synchronous or metachronous bilateral PHEOs (out of 112 PHEO patients who underwent surgery between 1976 and 2021). The median age at diagnosis was 32 years (9–76) (three were children). Nine patients (64.2%) presented synchronous bilateral tumors, five (35.7%) contralateral metachronous tumors, 2–12 years after the first surgical intervention; three (21.4%) were metastatic. Median follow-up: 5 years (1–41), IQR 19 months. A total of 78.5% had a germline mutation (eight RET gene with MEN2A syndrome, three VHL syndrome, three not tested). Post-surgery recurrence was noted in 16.6% of patients (one with MEN2A syndrome and metastatic PHEOs, one with VHL syndrome), with similar rates after total adrenalectomy or cortical-sparing adrenal surgery. AI was avoided in 40% after cortical-sparing surgery.
Conclusion
Bilateral PHEOs are usually associated with genetic syndromes. The surgical technique for patients with hereditary bilateral PHEOs should be chosen based on a personalized approach, as they are at higher risk for developing new adrenal tumors requiring additional surgeries.
Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
Search for other papers by Margret J Einarsdottir in
Google Scholar
PubMed
Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
Search for other papers by Penelope Trimpou in
Google Scholar
PubMed
Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
Search for other papers by Gudmundur Johannsson in
Google Scholar
PubMed
Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
Wallenberg Center for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
Search for other papers by Oskar Ragnarsson in
Google Scholar
PubMed
Objective
It is unknown whether glucocorticoid (GC)-induced adrenal insufficiency may cause premature mortality in GC users. We conducted a retrospective cohort study to investigate if undiagnosed and undertreated GC-induced adrenal insufficiency is a contributor to premature death in GC users.
Methods
Information on dispensed prescriptions in West Sweden from 2007 to 2014 was obtained from the Swedish Prescribed Drug Register. Cause of death was collected from the Swedish Cause of Death Register. Of 223,211 patients who received oral GC prescriptions, 665 died from sepsis within 6 months of their last prescription. Three hundred of these patients who had died in hospital were randomly selected for further investigation. Medical records were initially reviewed by one investigator. Furthermore, two additional investigators reviewed the medical records of patients whose deaths were suspected to be caused by GC-induced adrenal insufficiency.
Results
Of 300 patients (121 females, 40%), 212 (75%) were prescribed GC treatment at admission. The mean age was 76 ± 11 years (range 30–99). Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a probable contributor to death by at least two investigators in 11 (3.7%) patients. In five of these 11 cases, long-term GC therapy was abruptly discontinued during hospitalization. Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a possible contributing factor to death in a further 36 (12%) patients.
Conclusion
GC-induced adrenal insufficiency is an important contributor to premature death in GC users. Awareness of the disorder during intercurrent illness and following cessation of GC treatment is essential.
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia
Department of Endocrinology and Metabolism, BSMMU, Dhaka, Bangladesh
Search for other papers by Sharmin Jahan in
Google Scholar
PubMed
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia
Search for other papers by Jun Yang in
Google Scholar
PubMed
Search for other papers by Jinbo Hu in
Google Scholar
PubMed
Search for other papers by Qifu Li in
Google Scholar
PubMed
Search for other papers by Peter J Fuller in
Google Scholar
PubMed
Primary aldosteronism (PA) is the most common cause of endocrine hypertension and is often underdiagnosed. This condition is associated with increased cardiovascular morbidity and mortality in comparison to age and blood pressure matched individuals with essential hypertension (EH). The diagnostic pathway for PA consists of three phases: screening, confirmatory testing, and subtyping. The lack of specificity in the screening step, which relies on the aldosterone to renin ratio, necessitates confirmatory testing. The Endocrine Society’s clinical practice guideline suggests four confirmatory tests, including the fludrocortisone suppression test (FST), saline suppression test (SST), captopril challenge test (CCT), and oral sodium loading test (SLT). There is no universally accepted choice of confirmatory test, with practices varying among centers. The SST and FST are commonly used, but they can be resource-intensive, carry risks such as volume overload or hypokalemia, and are contraindicated in severe/uncontrolled HTN as well as in cardiac and renal impairment. In contrast, CCT is a safe and inexpensive alternative that can be performed in an outpatient setting and can be applied when other tests are contraindicated. Despite its simplicity and convenience, the variability in captopril dose, testing posture, and diagnostic threshold limit its widespread use. This narrative review evaluates the diagnostic accuracy of the CCT across different populations, addresses controversies in its usage, and proposes recommendations for its use in the diagnosis of PA. Furthermore, suggestions for future research aimed at promoting the wider utilization of the CCT as a simpler, safer, and more cost-effective diagnostic test are discussed.
Search for other papers by Magdalena Lech in
Google Scholar
PubMed
Search for other papers by Ruvini Ranasinghe in
Google Scholar
PubMed
Faculty of Life Sciences and Medicine, School of Life Course Sciences, King’s College London, London, UK
Search for other papers by Royce P Vincent in
Google Scholar
PubMed
Search for other papers by David R Taylor in
Google Scholar
PubMed
Search for other papers by Lea Ghataore in
Google Scholar
PubMed
Search for other papers by James Luxton in
Google Scholar
PubMed
Quebec Heart and Lung Institute, Laval University, Quebec, Canada
Search for other papers by Fannie Lajeunesse-Trempe in
Google Scholar
PubMed
Search for other papers by Pia Roser in
Google Scholar
PubMed
Search for other papers by Eftychia E Drakou in
Google Scholar
PubMed
Search for other papers by Ling Ling Chuah in
Google Scholar
PubMed
Barts and the London School of Medicine, Centre for Endocrinology, William Harvey Institute, London, UK
Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
Search for other papers by Ashley B Grossman in
Google Scholar
PubMed
Search for other papers by Simon J B Aylwin in
Google Scholar
PubMed
Obesity, Type 2 Diabetes and Immunometabolism Research Group, School of Cardiovascular and Metabolic Medicine & Sciences, Faculty of Life Course Sciences, King’s College London, London, UK
Division of Reproductive Health, Warwick Medical School, University of Warwick, Coventry, UK
Search for other papers by Georgios K Dimitriadis in
Google Scholar
PubMed
Introduction
Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex. Whilst surgery is the preferred treatment, adjunctive therapy with mitotane may be offered post-surgically to minimise the risk of recurrence or, in the absence of surgery, to attenuate progression.
Aim
The objective was to evaluate the effects of mitotane treatment on serum protein concentrations in patients treated for ACC with mitotane therapy and compare this to patients with other adrenal neoplasms and a normal pregnant cohort.
Methods
Serum cortisol, thyroid function tests, adrenocorticotrophic hormone (ACTH), cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG), gonadotrophins and androgens were measured on plasma and serum samples. Thirty-five patients with ACC were included, and mitotane levels were noted to be sub-/supra-therapeutic. Data were tested for normality, reported as mean ± s.d., and compared to other two cohorts using paired-sample t-test with a 5% P-value for significance and a 95% CI.
Results
Patients on mitotane therapy had a higher mean serum CBG concentration compared to the adrenal neoplasm group (sub-therapeutic: 79.5 (95% CI: 33.6, 125.4 nmol/L), therapeutic: 85.3 (95% CI: 37.1–133.6 nmol/L), supra-therapeutic: 75.7 (95% CI: −19.3, 170.6 nmol/L) and adrenal neoplasm: 25.5 (95% CI: 17.5, 33.5 nmol/L). Negative correlations between serum cortisol and CBG concentration were demonstrated within the supra-therapeutic plasma mitotane and adrenal neoplasm groups.
Conclusion
Patients with ACC and therapeutic plasma mitotane concentrations had higher serum CBG concentrations compared to those with adrenal neoplasms or pregnant women, and higher serum cortisol. Whilst there was no direct correlation with cortisol and mitotane level, the negative correlation of cortisol with CBG may suggest that the direct effect of mitotane in increasing cortisol may also reflect that mitotane has a direct adrenolytic effect.
Facultad de Medicina, Universidad Complutense de Madrid, Madrid, España
Search for other papers by Jorge Gabriel Ruiz-Sánchez in
Google Scholar
PubMed
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, España
Search for other papers by Alfonso Luis Calle-Pascual in
Google Scholar
PubMed
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España
Search for other papers by Miguel Ángel Rubio-Herrera in
Google Scholar
PubMed
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España
Search for other papers by María Paz De Miguel Novoa in
Google Scholar
PubMed
Search for other papers by Emilia Gómez-Hoyos in
Google Scholar
PubMed
Servicio de Endocrinología y Nutrición. Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clínico San Carlos, Madrid, España
Search for other papers by Isabelle Runkle in
Google Scholar
PubMed
Introduction
Hypoaldosteronism is characterized by hyperkalemia, and/or hypovolemic hyponatremia (HH), often accompanied by metabolic acidosis. HH is typical of hypoaldosteronism, whereas euvolemic hyponatremia (EH) is not. The purpose of the current study is to describe the characteristics of hyponatremia in hypoaldosteronism and elucidate whether EH can be considered part of the disease’s spectrum.
Methods
In a hypoaldosteronism cohort, we analyzed the factors associated with hyponatremia, comparing the characteristics of EH and HH and their associated factors. Correlation analyses of mineralocorticoid biomarkers, such as the transtubular potassium gradient (TTKG), the urinary Na+/K+ ratio (UNa+/UK+) with serum, and urinary electrolytes were performed in both types of hyponatremia.
Results
Of 112 hypoaldosteronism episodes, 77.7% were ≥65 years old, 44.6% were women, and 80 (71.4%) had hyponatremia. Hyponatremia was negatively associated with the presence of chronic kidney disease, and positively with a hypovolemic state, malnutrition, a prior history of hyponatremia, and glucocorticoid therapy. HH: 61/80 and EH: 19/80 episodes. HH was associated with an age ≥65 years and the use of diuretics, as well as factors related to an aldosterone deficit and/or mineralocorticoid resistance. In HH but not in EH, urinary potassium was correlated with the TTKG, and urinary sodium with both the TTKG and the UNa+/UK+.
Conclusion
Both HH and EH can be observed in hypoaldosteronism. However, only the former would be related to insufficient mineralocorticoid activity.
Significance statement
Isolated hypoaldosteronism is a poorly understood and underdiagnosed endocrinological disorder, classically recognized only when hyperkalemia is present. The development of hypovolemic hyponatremia, however, is also easily explained by the physiopathology of the disorder. The current study addresses the features of hyponatremia when found in the context of mineralocorticoid insufficiency, and confirms an association between hypovolemic hyponatremia and isolated hypoaldosteronism. Thus, the clinical spectrum of hypoaldosteronism is extended to include hypovolemic hyponatremia as a frequent manifestation of the disorder.
Search for other papers by Marianna Viukari in
Google Scholar
PubMed
Search for other papers by Helena Leijon in
Google Scholar
PubMed
Search for other papers by Tiina Vesterinen in
Google Scholar
PubMed
Search for other papers by Sanni Söderlund in
Google Scholar
PubMed
Search for other papers by Päivi Hämäläinen in
Google Scholar
PubMed
Search for other papers by Iina Yliaska in
Google Scholar
PubMed
Search for other papers by Päivi Rautiainen in
Google Scholar
PubMed
Search for other papers by Reeta Rintamäki in
Google Scholar
PubMed
Search for other papers by Minna Soinio in
Google Scholar
PubMed
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
Search for other papers by Ilkka Pörsti in
Google Scholar
PubMed
Search for other papers by Pasi I Nevalainen in
Google Scholar
PubMed
Search for other papers by Niina Matikainen in
Google Scholar
PubMed
Objective
The associations between adrenal histopathology, lateralization studies, and surgical outcomes in primary aldosteronism remain poorly characterized. We examined the value of immunohistochemical analysis of CYP11B2 for evaluation of adrenalectomy outcomes after anatomical versus functional subtyping.
Design
A retrospective multicenter study of 277 patients operated for primary aldosteronism who had an adrenalectomy sample available in the Finnish biobanks from 1 January 2000 to 31 December 2019. Adrenal slides from biobanks were analyzed centrally after CYP11B2 and CYP11B1 staining. Clinical data were obtained from patient registries. Histopathological diagnosis and cure after surgery were assessed as outcome measures.
Results
Re-evaluation with CYP11B2 staining changed the histopathological diagnosis in 91 patients (33%). The presence of a CYP11B2-positive adenoma and the use of functional subtyping independently predicted clinical cure of primary aldosteronism. CYP11B2-positive <7 mm nodules were more frequent in patients without clinical cure, whereas CYP11B2-positive micronodules were common in all patients and had no impact on adrenalectomy outcomes. Small CYP11B2-positive nodules and micronodules were equally prevalent regardless of the subtyping method applied. Clinical cure rates were lower and CYP11B2-negative adenomas more common after adrenalectomy based on anatomical imaging than functional studies.
Conclusions
Incorporating CYP11B2 staining in histopathological diagnosis enhances the prediction of surgical outcomes in primary aldosteronism. A finding of CYP11B2-positive adenoma is indicative of cure of primary aldosteronism, whereas smaller CYP11B2-positive nodules associate with poorer results at postoperative evaluation. Functional subtyping methods decrease the operations of CYP11B2-negative adenomas and are superior to anatomical imaging in identifying unilateral primary aldosteronism.
